Proparglyamines are frequent skeletons and synthetically-versatile key intermediates for the preparation of many nitrogen-containing biologically active compounds. In recent years, the most useful methods for synthesis of aminopropynes include using very sensitive Grignard reagent HCCMgBr and metal catalyzed propargylic substitution reactions with propargylic acetates, propargylic alcohols and propargylic halides. However, the organic alkynes used in aldehyde, alkyne and amine coupling or alkyne, halide and amine coupling processes are generally limited to substituted terminal alkynes, and when used, produce proparglyamines with internal alkynes which tend to limit many further important applications of functionalized alkynes.
Enaminones as synthetic chemical-intermediates have received considerable attention in recent years. This is attributed to their pronounced versatility in having the ability to participate as both electrophiles and nucleophiles in chemical reactions. While the earlier uses of enaminones were limited to serving as synthetic intermediates in organic synthesis, recent exploration for the various applications of enaminones in the valuable development of pharmaceutical products has made impressive progress.
A wide range of methods have been established to develop enaminones. Namely, these methods include condensation or addition reactions, the cleaving of heterocycles and the acylation of enaminones.
The most commonly-utilized method for the synthesis of enaminones involves the reaction between ammonia or a primary or secondary amine and a 1,3-diketone or 3-keto-ester. Occasionally this strategy can fail, for example, in the use of weak bases like those of o- or p-nitroaniline.
Generally, the preceding described methods to developing enaminones or proparglyamines either require highly-specific starting materials or relatively non-facile reactive conditions to facilitate the obtainment of either the desired enaminones or proparglyamines. Furthermore, in many instances, the final product yield of enaminones or proparglyamines may not be satisfactory.
There is a need to provide a process for producing an aminopropyne (or propargylamine) that overcomes, or at least ameliorates, one or more of the disadvantages described above.
There is also a need to provide a process for producing an enaminone.